Mucociliary clearance of inhaled particles from the tracheobronchial tree is an important defence mechanism of the lung. A failure of this clearance mechanism in disease probably results in retained mucous secretions and a predisposition to pulmonary infection. Circumstantial evidence indicates that airway secretion of ions, water, and mucus is an important factor in determining the rate of mucociliary clearance. Since the normal and abnormal physiology of these important secretory processes is only partially known, my proposal is to study the interrelationship among these processes. In other epithelia, water movement occurs in response to osmotic gradients created by the active transport of ions. Previously, we have shown that there is a predominant chloride ion pumped directed toward the tracheal lumen and a smaller sodium ion pump facing in the opposite direction. We will develop a technique to measure water movement, in vitro, across dog tracheal epithelium and will attempt to correlate the changes in ion transport and the electrical properties of the epithelium due to acetylcholine, terbutaline, histamine and changes in calcium concentration with water movement across the tracheal epithelium. Additionally, we will develop a technique to measure water and mucus secretion simultaneously, in vitro, in the dog tracheal epithelium, and we will use various agents (e.g., acetylcholine, terbutaline histamine and changes in calcium concentration) to alter water and/or mucus secretion in order to better define the interrelationship between these two processes.